Evaluation of the Thermal, Chemical, Mechanical, and Microbial Stability of New Nanohybrids Based on Carboxymethyl-Scleroglucan and Silica Nanoparticles for EOR Applications.

Scleroglucan (SG) is resistant to harsh reservoir conditions such as high temperature, high shear stresses, and the presence of chemical substances. However, it is susceptible to biological degradation because bacteria use SG as a source of energy and carbon. All degradation effects lead to viscosity loss of the SG solutions, affecting their performance as an enhanced oil recovery (EOR) polymer. Recent studies have shown that nanoparticles (NPs) can mitigate these degradative effects. For this reason, the EOR performance of two new nanohybrids (NH-A and NH-B) based on carboxymethyl-scleroglucan and amino-functionalized silica nanoparticles was studied. The susceptibility of these products to chemical, mechanical, and thermal degradation was evaluated following standard procedures (API RP 63), and the microbial degradation was assessed under reservoir-relevant conditions (1311 ppm and 100 °C) using a bottle test system. The results showed that the chemical reactions for the nanohybrids obtained modified the SG triple helix configuration, impacting its viscosifying power. However, the nanohybrid solutions retained their viscosity during thermal, mechanical, and chemical degradation experiments due to the formation of a tridimensional network between the nanoparticles (NPs) and the SG. Also, NH-A and NH-B solutions exhibited bacterial control because of steric hindrances caused by nanoparticle modifications to SG. This prevents extracellular glucanases from recognizing the site of catalysis, limiting free glucose availability and generating cell death due to substrate depletion. This study provides insights into the performance of these nanohybrids and promotes their application in reservoirs with harsh conditions.

Experimental Investigation of the Viscosity and Stability of Scleroglucan-Based Nanofluids for Enhanced Oil Recovery.

Biopolymers emerge as promising candidates for enhanced oil recovery (EOR) applications due to their molecular structures, which exhibit better stability than polyacrylamides under harsh conditions. Nonetheless, biopolymers are susceptible to oxidation and biological degradation. Biopolymers reinforced with nanoparticles could be a potential solution to the issue. The nanofluids' stability and performance depend on the nanoparticles' properties and the preparation method. The primary objective of this study was to evaluate the effect of the preparation method and the nanoparticle type (SiO2, Al2O3, and TiO2) on the viscosity and stability of the scleroglucan (SG). The thickening effect of the SG solution was improved by adding all NPs due to the formation of three-dimensional structures between the NPs and the SG chains. The stability test showed that the SG + Al2O3 and SG + TiO2 nanofluids are highly unstable, but the SG + SiO2 nanofluids are highly stable (regardless of the preparation method). According to the ANOVA results, the preparation method and standing time influence the nanofluid viscosity with a statistical significance of 95%. On the contrary, the heating temperature and NP type are insignificant. Finally, the nanofluid with the best performance was 1000 ppm of SG + 100 ppm of SiO2_120 NPs prepared by method II.

Carboxymethyl Scleroglucan Synthesized via O-Alkylation Reaction with Different Degrees of Substitution: Rheology and Thermal Stability.

This paper presents the methodology for synthesizing and characterizing two carboxymethyl EOR-grade Scleroglucans (CMS-A and CMS-B). An O-Alkylation reaction was used to insert a hydrophilic group (monochloroacetic acid-MCAA) into the biopolymer's anhydroglucose subunits (AGUs). The effect of the degree of the carboxymethyl substitution on the rheology and thermal stability of the Scleroglucan (SG) was also evaluated. Simultaneous thermal analysis (STA/TGA-DSC), differential scanning calorimetry (DSC), X-ray Diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Scanning Electron Microscopy, and Energy Dispersive Spectroscopy (SEM/EDS) were employed to characterize both CMS products. FTIR analysis revealed characteristic peaks corresponding to the carboxymethyl functional groups, confirming the modification. Also, SEM analysis provided insights into the structural changes in the polysaccharide after the O-Alkylation reaction. TGA results showed that the carboxymethylation of SG lowered its dehydroxylation temperature but increased its thermal stability above 300 °C. The CMS products and SG exhibited a pseudoplastic behavior; however, lower shear viscosities and relaxation times were observed for the CMS products due to the breakage of the SG triple helix for the chemical modification. Despite the viscosity results, the modified Scleroglucans are promising candidates for developing new engineering materials for EOR processes.

Prosopis juliflora Seed Waste as Biochar for the Removal of Blue Methylene: A Thermodynamic and Kinetic Study.

In this work, we studied the methylene blue (MB) dye adsorption capacity on biochar derived from residues of Prosopis juliflora seed waste, a species found in the region of the tropical dry forest of Piojó in the Department of Atlántico, Colombia. The materials were obtained by pyrolysis at temperatures of 300, 500, and 700 °C. Biochar was characterized using Fourier transform infrared (FTIR), scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM-EDX), TGA, and Brunauer-Emmett-Teller (BET) techniques. The three biochar samples presented a macroporous, rough structure with pore size between 6 and 28 µm. The largest pore surface area observed was 1.28 m2/g for pyrolyzed biochar produced at 500 °C, larger than that of biochar produced at 700 °C, which was 0.83 m2/g. The adsorption results show that the maximum percentage of MB removal was 69%. According to SEM results, the material's pore sizes varied on average from 6 to 28 µm. We modeled MB adsorption on biomass through three different isotherm models. The Freundlich model was the best-fitting model for the removal of MB (K F = 1.447; 1/n = 0.352). The kinetic results showed that the pseudo-second-order model was the best-fitting model for the sorption process (q e = 2.94 mg/g; k 2 = 0.087 g/(mg/min-1)). Furthermore, the recycling test showed that the biochar did not change its adsorption capacity significantly. Finally, under the experimental conditions, the thermodynamic parameters indicated that the removal of MB using biochar was an endothermic and spontaneous process; all ΔG° values ranged from -2.14 to -0.95 kJ/mol; ΔH° was 23.54 kJ/mol and ΔS° was 79.5 J/mol.

Photophysical study and in vitro approach against Leishmania panamensis of dicloro-5,10,15,20-tetrakis(4-bromophenyl)porphyrinato Sn(IV).

Background: Photodynamic therapy activity against different biological systems has been reported for porphyrins. Porphyrin modifications through peripheral groups and/or by metal insertion inside the ring are main alternatives for the improvement of its photo-physical properties. In this study, we synthesized and characterized 5,10,15,20-tetrakis(4-bromophenyl)porphyrin and the dicloro-5,10,15,20-tetrakis(4-bromophenyl)porphyrinato Sn(IV). Methods: Metal-free porphyrin was synthesized using the Alder method, while the Sn(IV)-porphyrin complex was prepared by combining metal-free porphyrin with stannous chloride in DMF; the reaction yields were 47% and 64% respectively. Metal-free porphyrin was characterized by UV-Vis, FT-IR, ESI-mass spectrometry and 13C-NMR. Additionally, the Sn(IV) -porphyrin complex was characterized using UV-Vis and FT-IR. Cyclic voltammetry tests in four different solvents. The fluorescence quantum yield (Φ f) was measured using fluorescein as a standard, the singlet oxygen quantum yield (Φ D) was estimated using the standard 5,10,15,20-(tetraphenyl)porphyrin (H2TPP) and the quencher of singlet oxygen 1,3-diphenylisobenzofuran (DPBF). Results: UV-Vis assay showed typical Q and Soret bands for porphyrin and its metallo-porphyrin complex. Compounds showed photoluminescence at the visible range of electromagnetic spectrum. The inclusion of the metal in the porphyrin core changed the Φ f from 0.15 to 0.05 and the Φ D increased from 0.55 to 0.59. Finally, the effect of the compounds on the viability of L. panamensis was evaluated by means of the MTT test. The results showed that both compounds decreased the viability of the parasite; this inhibitory activity was greater under light irradiation; the porphyrin compound had IC 50 of 16.5 µM and the Sn(IV)-porphyrin complex had IC 50 of 19.2 µM. Conclusion: The compounds were synthesized efficiently, their characterization was carried out by different spectroscopy techniques and their own signals were evidenced for both structures, both compounds decreased the cell viability of L. panamensis.

Synthesis, crystal structure, Hirshfeld surface analysis and energy framework calculations of trans-3,7,9,9-tetra-methyl-10-(prop-2-yn-1-yl)-1,2,3,4,4a,9,9a,10-octa-hydro-acridine.

The title heterocyclic compound, C20H27N, has been prepared in good yield (72%) via a BiCl3-catalyzed cationic Povarov reaction between N-propargyl-4-methyl-aniline and (±)-citronellal. The X-ray single-crystal study indicates that the structure consists of mol-ecules connected by C-H⋯π contacts to produce chains, which pack in a sandwich-herringbone fashion along the b-axis direction. Hirshfeld surface analysis indicates that H⋯H inter-actions dominate by contributing 79.1% to the total surface. Energy frameworks and DFT calculations indicate a major contribution of dispersive forces to the total inter-action energy.

Importancia de los interferones tipo I en la respuesta inmune antiviral contra el Virus del Papiloma Humano / Importance of type I interferons in the antiviral immune response against the Human Papillomavirus

Resumen Los interferones (IFNs) son citoquinas fundamentales en la modulación de la inmunidad innata y adaptativa del hospedero, el papel de los IFNs tipo I en el control de la infección por el Virus del Papiloma Humano (VPH) es crucial para una eficiente respuesta antiviral del huésped. Esta revisión profundiza sobre las funciones de los IFNs tipo I en la infección causada por el VPH y los mecanismos de evasión de este virus para inactivar los IFNs tipo I, todos estos mecanismos necesarios para el desarrollo y progresión de lesiones malignas en los tejidos infectados por el VPH.

Abstract The interferons (IFNs) are very important cytokines in the interface between innate and adaptive immunity of the host, the role type I IFNs in the control of HPV is pivotal for an efficient immune response, so a wide knowledge about this topic will contribute understanding HPV pathogenicity mechanism. This review focuses on the HPV evasion mechanisms for the type I IFNs which are necessary for a malignant lesion development, otherwise develops knowledge about the type I IFNs functions on the HPV infection.

Morphological and Structural Properties of Amino-Functionalized Fumed Nanosilica and Its Comparison with Nanoparticles Obtained by Modified Stöber Method.

In industry, silica nanoparticles (NPs) are obtained by the fuming and the precipitation method. Fumed silica NPs are commonly used in the preparation of nanocomposites because they have an extremely low bulk density (160-190 kg/m3), large surface area (50-600 m2/g), and nonporous surface, which promotes strong physical contact between the NPs and the organic phase. Fumed silica has fewer silanol groups (Si-OH) on its surface than the silica prepared by the Stöber method. However, the number of -OH groups on the fumed silica surface can be increased by pretreating them with sodium hydroxide (NaOH) before further surface modification. In this study, the effectiveness of the NaOH pretreatment was evaluated on commercial fumed silica NPs with a surface area of 200 m2/g. The number of surface -OH groups was estimated by potentiometric titration. The pretreated fumed NPs, and the precipitated NPs (prepared by the Stöber method) were modified with 3-aminopropyltriethoxysilane (APTES) to obtain A200S and nSiO2-APTES, respectively. The NPs were characterized using electron dispersive scanning (EDS), scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), BET (Brunauer-Emmett-Teller) analysis, and ζ-potential. XRD confirmed the presence of the organo-functional group on the surface of both NPs. After the amino-functionalization, the ζ-potential values of the nSiO2 and A200 changed from -35.5 mV and -14.4 mV to +26.2 mV and +11.76 mV, respectively. Consequently, we have successfully synthesized functionalized NPs with interesting, specific surface area and porosity (pore volume and size), which can be attractive materials for chemical and energy industries.

New Nanohybrid Based on Hydrolyzed Polyacrylamide and Silica Nanoparticles: Morphological, Structural and Thermal Properties.

In this study, a set of advanced characterization techniques were used to evaluate the morphological, structural, and thermal properties of a novel molecular hybrid based on silica nanoparticles/hydrolyzed polyacrylamide (CSNH-PC1), which was efficiently obtained using a two-step synthetic pathway. The morphology of the nanohybrid CSNH-PC1 was determined using scanning electron microscopy (SEM), dynamic light scattering (DLS), and nanotracking analysis (NTA) techniques. The presence of C, N, O, and Si atoms in the nanohybrid structure was verified using electron dispersive scanning (EDS). Moreover, the corresponding structural analysis was complemented using powder X-ray diffraction (XRD) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR). The covalent bond between APTES-functionalized SiO2 nanoparticles (nSiO2-APTES), and the hydrolyzed polyacrylamide (HPAM) chain (MW ≈ 20.106 Da) was confirmed with high-resolution X-ray spectroscopy (XPS). Finally, the thermal properties of the nanohybrid were evaluated by using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The results showed that the CSNH-PC1 has a spherical morphology, with sizes between 420-480 nm and higher thermal resistance compared to HPAM polymers without modification, with a glass transition temperature of 360 °C. The integration of these advanced characterization techniques implemented here shows promising results for the study and evaluation of new nanomaterials with multiple applications.

In Vitro Anti-Leishmanial Effect of Metallic Meso-Substituted Porphyrin Derivatives against Leishmania braziliensis and Leishmania panamensis Promastigotes Properties.

In this study, a family of porphyrins based on 5,10,15,20-Tetrakis(4-ethylphenyl)porphyrin (1, Ph) and six metallo-derivatives (Zn2+(2, Ph-Zn), Sn4+(3, Ph-Sn), Mn2+ (4, Ph-Mn), Ni2+ (5, Ph-Ni), Al3+ (6, Ph-Al), and V3+ (7, Ph-V)) were tested as photosensitizers for photodynamic therapy against Leishmania braziliensis and panamensis. The singlet oxygen quantum yield value (ΦΔ) for (1-7) was measured using 1,3-diphenylisobenzofuran (DPBF) as a singlet oxygen trapping agent and 5,10,15,20-(tetraphenyl)-porphyrin (H2TPP) as a reference standard; besides, parasite viability was estimated by the MTT assay. After metal insertion into the porphyrin core, the ΦΔ increased from 0.76-0.90 and cell viability changed considerably. The ΦΔ and metal type changed the cytotoxic activity. Finally, (2) showed both the highest ΦΔ (0.90) and the best photodynamic activity against the parasites studied (IC50 of 1.2 µM).

Efficient synthesis and antioxidant activity of novel N-propargyl tetrahydroquinoline derivatives through the cationic Povarov reaction.

New N-propargyl tetrahydroquinolines 6a-g have been synthesized efficiently through the cationic Povarov reaction (a domino Mannich/Friedel-Crafts reaction), catalyzed by Indium (III) chloride (InCl3), from the corresponding N-propargylanilines preformed, formaldehyde and N-vinylformamide, with good to moderate yields. All tetrahydroquinoline derivatives obtained were evaluated in vitro as free radical scavengers. Results showed that compound 6c presents a potent antioxidant effect compared with ascorbic acid, used as a reference compound. ADME predictions also revealed favorable pharmacokinetic parameters for the synthesized compounds, which warrant their suitability as potentials antioxidant. Additionally, a theoretical study using Molecular Quantum Similarity and reactivity indices were developed to discriminate different reactive sites in the new molecules in which the oxidative process occurs.

Effects of new tetrahydroquinoline-isoxazole hybrids on bioenergetics of hepatocarcinoma Hep-G2 cells and rat liver mitochondria.

New molecular hybrids were synthesized by combining tetrahydroquinoline (THQ) and isoxazole (ISX) scaffolds, in search for chemical structures with improved pharmacological properties. Our tetrahydroquinoline (THQ) and isoxazole (ISX) hybrids differ in the X and Y substituents: FM53 (X = H; Y= H), FM49 (X = CH3; Y= OCH3), FM50 (X = Cl; Y= H) and FM48 (X = Cl; Y= OCH3). Aiming at exploring their bioactivity in liver cancer cells, in this paper we report the effect of four THQ-ISX hybrids on viability, respiration and oxidative stress in Hep-G2 human hepatoma cells. In addition, we measured the alterations induced by these compounds on oxygen uptake and respiratory chain enzymes in isolated mitochondria. Cell viability assay indicated that these THQ-ISX hybrids displayed antiproliferative activity on Hep-G2 cells. Among these, FM50 (IC50 = 5.2 ±â€¯1.9 µM) and FM53 (IC50 = 6.8 ±â€¯0.7 µM) had the highest cytotoxicity. These four hybrids also inhibited the Hep-G2 cells respiration in the uncoupled state, with FM50 decreasing all respiratory states (basal, leak, uncoupled). While only FM49 and FM53 altered the Hep-G2 cells redox function. In terms of mitochondrial bioenergetics, THQ-ISX hybrids decreased the oxygen consumption in state 3 (via complex I and II), and also inhibited NADH oxidase and NADH cytochrome c reductase enzyme activities. In these experiments, the structural homologues FM50 and FM53 had a remarkable inhibitory effect (~50%) with respect to FM49 and FM48. These results show that THQ-ISX hybrids are promising compounds for hepatoma cancer treatment and that the phenyl substituent (Y= H) in the ISX scaffold intensifies both, the cytotoxicity in Hep-G2 cells and, inhibition of electron transport through complex I of the mitochondrial respiratory chain.

Facile and highly diastereo and regioselective synthesis of novel octahydroacridine-isoxazole and octahydroacridine-1,2,3-triazole molecular hybrids from citronella essential oil.

A novel and highly efficient synthetic approach for the expedite construction of new octahydroacridine-isoxazole- and octahydroacridine-1,2,3-triazole-based molecular hybrids is first reported. Rapid access to the octahydroacridine core was achieved in a highly diastereoselective fashion via cationic Povarov reaction of N-propargyl anilines and citronella essential oil (Cymbopogon nardus). The subsequent 1,3-dipolar and Cu (I) catalyzed alkyne-azide cycloaddition reaction of the terminal alkyne fragment with the corresponding oxime or azide affords the desired 3,5-isoxazoles and 1,2,3-triazoles, respectively, as interesting molecular hybrid models for pharmacological studies.

Novel N-allyl/propargyl tetrahydroquinolines: Synthesis via Three-component Cationic Imino Diels-Alder Reaction, Binding Prediction, and Evaluation as Cholinesterase Inhibitors.

New N-allyl/propargyl 4-substituted 1,2,3,4-tetrahydroquinolines derivatives were efficiently synthesized using acid-catalyzed three components cationic imino Diels-Alder reaction (70-95%). All compounds were tested in vitro as dual acetylcholinesterase and butyryl-cholinesterase inhibitors and their potential binding modes, and affinity, were predicted by molecular docking and binding free energy calculations (∆G) respectively. The compound 4af (IC50 = 72 µm) presented the most effective inhibition against acetylcholinesterase despite its poor selectivity (SI = 2), while the best inhibitory activity on butyryl-cholinesterase was exhibited by compound 4ae (IC50 = 25.58 µm) with considerable selectivity (SI = 0.15). Molecular docking studies indicated that the most active compounds fit in the reported acetylcholinesterase and butyryl-cholinesterase active sites. Moreover, our computational data indicated a high correlation between the calculated ∆G and the experimental activity values in both targets.

Synthesis and in vitro Evaluation of Antifungal Properties of Some 4-Aryl-3-Methyl-1,2,3,4-Tetrahydroquinolines Derivatives / Síntesis y evaluación in vitro de las propiedades antifungicas de algunos derivados de 4-aril-3-metil-1,2,3,4-tetrahidroquinolinas / Síntese e avaliação in vitro das propriedades antifungicas de alguns derivados de 4-Aryl-3-Methyl-1,2,3,4-Tetrahydroquinolines

Two series of 4-aryl-3-methyl-1,2,3,4-tetrahydroquinoline derivatives were efficiently synthesized according to a two-step synthesis and evaluated as potential antifungal agents. The key step was the formation of the corresponding N-benzyltetrahydroquinolines 5 via a three-component cationic imino Diels-Alder cycloaddition. The second step was a catalytic debenzylation to obtain the N-unprotected tetrahydroquinolines 6. The products were isolated and purified by column chromatography. Substances were characterized using nuclear magnetic resonance (NMR) mass spectrometry (MS) and infrared spectroscopy (IR). All compounds were tested in vitro against standardized, clinically important fungi, including yeasts, hialohyphomycetes, and dermatophytes. These studies showed that between the tetrahydroquinoline series tested, compounds 6f and 6g showed antifungal activity, specifically against dermatophytes. The compound 6-methoxy-4-(4-hydroxi-3-methoxyphenyl)-3-methyl-1,2,3,4-tetrahydroquinoline 6g exhibited the best in vitro activity (MIC 32-65 μg/mL). The results indicated that the elimination of benzyl group from the N-benzyltetrahydroquinolines derivatives, as well as the introduction of a hydroxyl group in the 4-aryl substituent caused a significant improvement in the antifungal activity. These results were supplemented by the in silico prediction; most of the tetrahydroquinolines evaluated showed high bioavailability, high drugs score and low potential risk.

Dos series de 4-aril-3-metil-1,2,3,4-tetrahidroquinolinas fueron sintetizadas de acuerdo con una metodología sintética de dos pasos y evaluadas como potenciales agentes antifúngicos. El paso clave involucró la formación de las correspondientes N-bencil tetrahidroquinolinas 5 vía una cicloadición imino Diels-Alder catiónica. El segundo paso consistió en obtener las tetrahidroquinolinas N-desprotegidas 6 vía una desbencilación catalítica. Los productos fueron aislados y purificados usando cromatografía en columna (CC). Las sustancias fueron identificadas usando resonancia magnética nuclear (RMN), espectrometría de masas (EM) y espectroscopia infrarroja (IR). Los compuestos fueron evaluados in vitro frente a cepas estandarizadas de hongos clínicamente relevantes, incluyendo levaduras, hialohifomicetes y dermatofitos. Estos estudios mostraron que, de las tetrahidroquinolinas ensayadas, los compuestos 6f y 6g mostraron actividad antifúngica, específicamente frente a dermatofitos. El compuesto 6-metoxi-4-(4-hidroxi-3-metoxifenil)-3-metil-1,2,3,4-tetrahidroquinolina 6g exhibió la mejor actividad (MIC 32-65 μg/mL). Los resultados indican que remover el grupo bencilo e introducir un grupo hidroxilo en el sustituyente arilo de las N-bencil tetrahidroquinolinas produce un mejoramiento de la actividad antifúngica. Predicciones in silico complementaron los resultados: la mayoría de las tetrahidroquinolinas ensayadas mostraron alta biodisponibilidad, altos "drug scores" y bajo riesgo potencial.

Duas séries de 4-aril-3-metil-1,2,3,4-tetrahidroquinolina foram sintetizadas de acordo com um método de síntese em duas etapas e avaliadas como potenciais agentes antifúngicos. O passo chave envolveu a formação dos correspondentes N-bencil tetrahidroquinolinas 5 via uma cicloadição de imino Diels-Alder catiónica. O segundo passo foi obter as N-tetrahidroquinolinas 6 através de uma desbenzilação catalítica. Os produtos foram purificados utilizando cromatografia em coluna. As substancias foram identificadas por ressonancia magnética nuclear (RMN), espectrometria de massa (EM) e espectroscopia de infravermelho (IR). Todos o compostos foram testados in vitro contra as estirpes padrao e os fungos clinicamente importantes, incluindo as leveduras, hialohifomicetes e dermatófitos. Estes estudos mostraram que entre a série de tetrahidroquinolinas (THQ) os compostos 6f e 6g mostraram atividade antifúngica, particularmente contra dermatófitos. O composto 6-metoxi-4-(4-hidroxi-3-metoxifenil)-3-metil-1,2,3,4-tetrahidroquinila 6g mostrou melhor atividade (MIC 32-65 μg/mL). Os resultados indicam que a remoção do grupo benzilo e a introdujo de um grupo hidroxilo no substituinte arilo do N-benzil-tetrahidroquinolina, resultou num aumento significativo da atividade antifúngica. Os resultados foram suplementados por previsöes in silico, que mostraram alta biodisponibilidade e pouco risco potencial da maioria dos tetrahidroquinolinas avaliados.

In vitro activity of synthetic tetrahydroindeno[2,1-c]quinolines on Leishmania mexicana.

New synthetic compounds based on tetrahydroindenoquinoline structure were evaluated for their in vitro antileishmanial activities. The seven compounds assayed have antiproliferative activities against promastigotes of Leishmania mexicana. Compound 1 and 3 were the most active (IC50 1.0 µg/ml) and showed high selectivity towards the parasite. These compounds were selected to evaluate their effect on promastigote morphology and mitochondrial transmembrane potential as well as on the amastigote capability to survive into macrophages J774 cell line. Whereas compound 1 affected the promastigote cell cycle, compound 3 induced morphological changes and the total collapse of the mitochondrial transmembrane potential, a hallmark of apoptosis. Both compounds also affected the amastigote form of the parasite, decreasing their survival rate in J774 macrophages. Due to the greatest selectivity index, the apparent effect as apoptotic inducer and its sustained inhibition on intracellular amastigote replication, compound 3 is the best candidate to be tested in vivo. This compound is worth considering for the development of new antileishmanial drugs.

Selective activity of 2,4-diaryl-1,2,3,4-tetrahydroquinolines on Trypanosoma cruzi epimastigotes and amastigotes expressing ß-galactosidase.

The growth inhibitory effect on Trypanosoma cruzi epimastigotes and the unspecific cytotoxicity over NCTC-929 fibroblasts of two series of previously synthesized 2,4-diaryl-1,2,3,4-tetrahydroquinolines (THQ), have been studied in vitro and compared with those of benznidazole (BZ). Derivatives AR39, AR40, AR41, AR91 and DM15 achieved outstanding selectivity indexes (SI) on the extracellular form (SITHQ>SIBZ>9.44) and thus, were tested in a more specific in vitro assay against amastigotes, showing less effectiveness than the reference drug (SIBZ>320) but also accomplishing great selectivity on the intracellular stage (SITHQ>25). These promising results, supported by the in silico prediction of high bioavailability and less potential risk than benznidazole, reveal several tetrahydroquinolines as prototypes of potential antichagasic drugs.

Synthesis and Crystal Structure of Two Nitro-Regioisomers of cis-4(4-Methoxyphenyl)-3-Methyl-2-Phenyl-1, 2, 3, 4-Tetrahydroquinoline / Síntesis y estudio de la estructura cristalina de dos nitro regioisómerosde la cis-4-(4-metoxifenil)-3-metil-2-fenil-1, 2, 3, 4-tetrahydroquinolina

Dos nitro-regioisómeros de la moléculacis-4-(4-metoxifenil)-3-metil-2-fenil-1,2,3,4-tetrahydroquinolina fueronpreparados vía una síntesis one-pot de tres componentes basada en lareacción de cicloadición imino Diels-Alder catalizada por BF3.OEt2. Sucompleta caracterización estructural se llevó a cabo usando la técnicade difracción de rayos-X de monocristal y métodos espectroscópicos.La pureza de los productos y la composición de las mezclas de reacciónfueron monitoreadas por cromatografía en capa fina (CCD). Losproductos fueron aislados y purificados usando cromatografía encolumna. Las sustancias fueron identificadas usando resonancia magnéticanuclear (RMN) y espectrometría de masas (EM). Los datos para lacaracterización por difracción de rayos-X fueron colectados usando undifractómetro Bruker AFC7S Mercury con radiación de Mo-Kα (λ =0.71073Å) a temperatura ambiente. Las estructuras de los regio-isómerosfueron confirmadas por 1H RMN y 13C RMN y la estructura cristalinafue estudiada usando la difracción de rayos-X de monocristal. El análisisespectroscópico (RMN, EM y difracción de rayos-X) mostró una completacaracterización y permitió establecer la correcta estereoquímica para elanillo tetrahidroquinolínico. El empaquetamiento molecular en el cristalpara el regioisómero 5-nitro 4 es producto de la combinación de enlaces dehidrógeno intermoleculares e interacciones de van der Waals, mientras queen el 7-nitro regioisómero 3 el empaquetamiento se debe principalmente ainteracciones intermoleculares débiles de tipo van der Waals y N—H••• π...

Here we synthesized two nitro regioisomersof cis-4-(4-methoxyphenyl)-3-methyl-2-phenyl-1,2,3,4-tetrahydroquinoline via the “one pot” three-componentimino Diels-Alder reaction catalyzed by BF3.OEt2and completed its structural characterization using thesingle crystal X-ray diffraction technique and otherspectroscopic methods. To monitor the purity of theproducts and the composition of the reaction mixtureswe used thin layer chromatography, and isolated andpurified the products by column chromatography. Thenusing nuclear magnetic resonance (NMR) and massspectrometry (MS) identified the substances. We collectedX-ray diffraction data for crystal characterization byusing a Bruker AFC7S Mercury diffractometer with Mo-Kα radiation (λ = 0.71073Å) at room temperature. Thestructures of these regioisomers were confirmed by 1HNMR and 13C NMR studies and studied their crystalstructure using single crystal X-ray diffraction technique.The spectroscopy analyses (NMR, GC-MS and X-raydiffraction) provided a complete characterizationand enabled the correct stereochemistry for thetetrahydroquinoline ring. We determined the molecularpacking for the 5-nitro regioisomer 4 is the product ofthe combination of intermolecular hydrogen bonds andvan der Waals interactions, while for 7-nitro regioisomer3 is mainly due to weak intermolecular van der Waalsinteractions and N—H··· π...

Dois nitro regioisómeros da molécula cis-4-(4-metoxifenil)-3-metil-2-fenil-1,2,3,4-tetrahydroquinolina foram preparados através de umasíntese de um só recipiente de três componentes com base na reacçãode imino Diels-Alder cicloadição catalisada BF3.OEt2 e sua completacaracterização estrutural foi realizada usando a técnica de difracçãocristalografia de raios X, e outros métodos espectroscópicos. A purezado produto e a composição das misturas reaccionais foram monitorizadaspor cromatografia em camada fina (CCD). Os produtos foram isoladose purificados utilizando cromatografia em coluna. As substâncias foramidentificadaos por ressonância magnética nuclear (RMN) e espectrometriade massa (EM). Os dados para caracterização por difração de raios Xforam coletados usando um Bruker AFC7S Mercury difratômetro comMo-Ka radiação (λ = 0,71073Å) à temperatura ambiente. As estruturasdosa regioisómeros foram confirmadaos por 1H RMN e 13C RMN aestrutura de cristal foi investigada usando difracção de raios X de cristalúnico. As análises espectroscópicas (RMN, EM e difracção de raios-X)demonstraram uma completa caracterização e permitiramu estabelecer aestereoquímica correcta de anel tetrahidroquinolínico. O empacotamentomolecular no cristal para 5-nitro regioisómero 4 é derivado de umacombinação de ligações de hidrogénio intermoleculares e interacções devan der Waals, e ao 7-nitro regioisómero 3 embalagens é principalmentedevido a interacções intermoleculares fracas do tipo van der Waals e N-H• • • π...

Identification in silico and in vitro of novel trypanosomicidal drug-like compounds.

Atom-based bilinear indices and linear discriminant analysis are used to discover novel trypanosomicidal compounds. The obtained linear discriminant analysis-based quantitative structure-activity relationship models, using non-stochastic and stochastic indices, provide accuracies of 89.02% (85.11%) and 89.60% (88.30%) of the chemicals in the training (test) sets, respectively. Later, both models were applied to the virtual screening of 18 in-house synthesized compounds to find new pro-lead antitrypanosomal agents. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Predictions agree with experimental results to a great extent (16/18) of the chemicals. Sixteen compounds show more than 70% of epimastigote inhibition at a concentration 100 µg/mL. In addition, three compounds (CRIS 112, CRIS 140 and CRIS 147) present more than 70% of epimastigote inhibition at a concentration of 10 µg/mL (79.95%, 73.97% and 78.13%, respectively) with low values of cytotoxicity (19.7%, 7.44% and 20.63%, correspondingly).Taking into account all these results, we could say that these three compounds could be optimized in forthcoming works. Even though none of them resulted more active than nifurtimox, the current results constitute a step forward in the search for efficient ways to discover new lead antitrypanosomals.